Pancreatic Cancer
Conditions
Keywords
vaccine, immunotherapy, antibody, PD-1, radiation
Brief summary
This study will be looking at whether combining cyclophosphamide, pembrolizumab (an antibody that blocks negative signals to T cells), GVAX (pancreatic cancer vaccine), and SBRT (focused radiation) is effective (anti-tumor activity) and safe in patients with locally advanced pancreatic cancer.
Interventions
DRUGCyclophosphamide
200 mg/m2 is to be administered as a 30 minute IV infusion one day prior to GVAX Pancreas Vaccine every 21 days for a total of 8 doses. In the extended treatment phase, eligible patients may receive 200 mg/m2 as a 30 minute IV infusion one day prior to GVAX Pancreas Vaccine every 6 months for an additional 4 doses.
2.5E8 cells of each cell line (Panc 6.03/Panc 10.05) for a total of 5E8 cells is to be administered one day after CY and pembrolizumab for a total of 8 doses. In the extended treatment phase, eligible patients may receive 2.5E8 cells of each cell line (Panc 6.03/Panc 10.05) for a total of 5E8 cells administered one day after CY every 6 months for an additional 4 doses.
DRUGPembrolizumab
200 mg will be administered as a 30 minute IV infusion one day prior to the GVAX pancreas vaccine every 21 days for a total of 8 doses. In the extended treatment phase, eligible patients may receive 200 mg as a 30 minute IV infusion every 21 days for an additional 9 doses.
RADIATIONSBRT
Patients will receive SBRT (6.6 Gy for 5 days) with the second dose of combined immunotherapy (CY/Pembrolizumab/GVAX Pancreas Vaccine).
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Locally advanced pancreatic adenocarcinoma 2. Patients must have received mFOLFIRINOX or Gemcitabine/ Abraxane based chemotherapy for 4 cycles with last dose of therapy between 2-5 weeks of study enrollment. 3. Age \>18 years 4. No metastatic disease 5. ECOG Performance Status of 0 to 1 6. Adequate organ function as defined by study-specified laboratory tests 7. Patients must be able to have fiducials placed for SBRT 8. Must use acceptable form of birth control through the study 9. Signed informed consent form 10. Willing and able to comply with study procedures
Exclusion criteria
1. Patients who have been off of mFOLFIRINOX or gemcitabine/abraxane therapy for more than 49 days 2. Patients who have had more than one line of chemotherapy 3. Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements 4. Patient who have had prior treatment with IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies 5. Patients receiving active immunosuppressive agents or chronic use of systemic corticosteroids within 14 days prior to first dose of study drug 6. Patients who have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 14 days of study drug administration 7. Patients with history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematous (SLE) autoimmune vasculitis, CNS or motor neuropathy considered to be of autoimmune origin. 8. Patients who have known history of infection with HIV, hepatitis B, or hepatitis C 9. Patients with evidence of interstitial lung disease 10. Patients on home oxygen 11. Patients with oxygen saturation of \<92% on room air by pulse oximetry 12. Pregnant or lactating 13. Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Distant Metastasis Free Survival (DMFS) | 62 months | DMFS is defined as the duration of time from start of treatment to identification of distant metastases on imaging or death, whichever occurs first. Estimation based on the Kaplan-Meier curve. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing a Grade 3 or Above Treatment Related Toxicities | 41 months | When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORValerie Lee, MD
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cyclophosphamide, Pembrolizumab, GVAX Pancreas Vaccine, SBRT Cyclophosphamide: 200 mg/m2 is to be administered as a 30 minute IV infusion one day prior to GVAX Pancreas Vaccine every 21 days for a total of 8 doses. In the extended treatment phase, eligible patients may receive 200 mg/m2 as a 30 minute IV infusion one day prior to GVAX Pancreas Vaccine every 6 months for an additional 4 doses.
GVAX Pancreas Vaccine: 2.5E8 cells of each cell line (Panc 6.03/Panc 10.05) for a total of 5E8 cells is to be administered one day after CY and pembrolizumab for a total of eight doses. In the extended treatment phase, eligible patients may receive 2.5E8 cells of each cell line (Panc 6.03/Panc 10.05) for a total of 5E8 cells administered one day after CY every 6 months for an additional 4 doses.
Pembrolizumab: 200 mg will be administered as a 30 minute IV infusion one day prior to the GVAX pancreas vaccine every 21 days for a total of 8 doses. In the extended treatment phase, eligible patients may receive 200 mg as a 30 minute IV infusion every 21 days for an additional 9 doses.
SBRT: Patients will receive SBRT (6.6 Gy for 5 days) with the second dose of combined immunotherapy (CY/Pembrolizumab/GVAX Pancreas Vaccine). | 58 |
| Total | 58 |
Baseline characteristics
| Characteristic | Cyclophosphamide, Pembrolizumab, GVAX Pancreas Vaccine, SBRT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 32 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 49 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 44 / 58 |
| other Total, other adverse events | 54 / 58 |
| serious Total, serious adverse events | 6 / 58 |
Outcome results
Primary
Distant Metastasis Free Survival (DMFS)
DMFS is defined as the duration of time from start of treatment to identification of distant metastases on imaging or death, whichever occurs first. Estimation based on the Kaplan-Meier curve.
Time frame: 62 months
Population: All patients who have received at least two doses of immunotherapy and have had their disease re-evaluated with imaging will be considered evaluable for response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cyclophosphamide, Pembrolizumab, GVAX Pancreas Vaccine, SBRT | Distant Metastasis Free Survival (DMFS) | 9.8 months |
Secondary
Number of Participants Experiencing a Grade 3 or Above Treatment Related Toxicities
When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.
Time frame: 41 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cyclophosphamide, Pembrolizumab, GVAX Pancreas Vaccine, SBRT | Number of Participants Experiencing a Grade 3 or Above Treatment Related Toxicities | 11 Participants |